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Simultaneous infection of immunocompetent individuals with multiple cytomegalovirus strains
CORRESPONDENCE
based medicine, but such an approach seems like a step backward. *Bertil Lindmark, Anders Ottosson Astra Draco AB, Department of Clinical Drug Safety and Epidemiology, PO Box 34, S-221 00 Lund, Sweden 1 2
Jenne JW. Can oral 2 agonists cause heart failure. Lancet 1998; 352: 1081–82. Martin MM, Dunn NR, Freemantle SN, Mann RD. Risk of non-fatal cardiac failure and ischaemic heart disease with long acting 2 agonists. Thorax 1998; 53: 558–62.
Adverse effects of human insulin Sir—With respect to your Aug 29 editorial,1 we represent people with insulin-dependent diabetes who have difficulties with genetically produced human insulin which largely regress with a change to natural animals insulins. These adverse effects have not been generally recognised by the medical profession, and despite the absence of large scale randomised controlled trials human insulin has become first-line treatment. It is noteworthy, however, that in the past year the Medicines Control Agency (MCA) has provided more information and in a more helpful way. We believe that there are several possible reasons for this change: a policy of open government; the threat of a Freedom of Information Act; the fact that we can often obtain information from the European Evaluation Agency; or a change in government or staff. The information held by the MCA from premarketing trials would be of real benefit in evaluating the adverse reactions to human insulin, but we have been unable to elicit these data from the MCA in more than 4 years. During our lobbying for a change in the Medicines Act 1968 to allow freedom of information to apply to medicines, we received a letter from the Baroness Hayman, dated Aug 19, 1998, stating that “The CSM concluded that some patients did experience problems with human insulin, particularly when initially transferred from animal insulins, and were better suited to continuing their treatment with animal insulins”. At no time during our years of correspondence with the MCA has such a statement been made, even though the number of reported adverse reactions to human insulin is more than five times greater than for the combined total for bovine and porcine insulins. Nor is there evidence that human insulin has any greater benefit than animal insulins. Further, omitting to make public the CSM conclusions has
1710
resulted in a failure to address the cost/benefit relation in the prescribing of insulins. In 1995, we pointed out to the Department of Health that our conservative estimate for prescribing human insulin was costing the NHS an extra £19 million per year. This figure has clearly risen since then with the introduction of disposable pens for human insulin, and with the cost of treating the adverse reactions. This selective provision of information by the MCA and failure to make public the information they have affects not only the health and wellbeing of patients but also the public purse at a time when our health service is struggling financially. Jenny Hirst Insulin Dependent Diabetes Trust, PO Box 294, Northampton NN3 2BN, UK 1
Anon. Freedom of information, when it suits. Lancet 1998; 352: 665.
Simultaneous infection of immunocompetent individuals with multiple cytomegalovirus strains Sir—Ursula Meyer-König and colleagues (Oct 17, p 1280)1 report that several human cytomegalovirus (HCMV) glycoprotein-B variants might be latent in different tissue of one healthy individual and that the analysis of HCMV strain variability at a single site of the glycoprotein-B gene was insufficient. However, the clinical importance of latent simultaneous infection of healthy people with multiple HCMV strains remains unclear. HCMV has been classified into four glycoprotein-B genotypes, according to restriction-fragment-length polymorphism of the variable site of the gene.2 Viraemia caused by glycoproteinB group 2 HCMV strain was associated with higher risk of HCMV retinitis than viraemia due to other glycoprotein-B groups.3 We analysed 33 clinical isolates of HCMV from immunocompetent children less than 2 years of age. HCMV from urinary samples was isolated by the standard tissue-culture technique that uses MRC-5 cells. The presence of HCMV was confirmed by observation of its characteristic cytopathic effect and by immunofluorescent staining with monoclonal antibodies against HCMV immediateearly and early antigen. DNA was extracted from MRC-5 cells, and we amplified HCMV glycoprotein-B gene with PCR assay according to Chou’s
method.2,3 The amplified fragment that contained glycoprotein-B gene was digested in parallel with two endonucleases, Hha I and Rsa I. Among 33 clinical isolates, 24 were identified as glycoprotein-B group 1, one as group 2, six as group 3, and two as simultaneous infection of group 1 and group 3. We did not identify glycoprotein-B group 4 from our samples. There were no differences in clinical appearances between HCMV glycoprotein-B groups 1 to 3. Simultaneous infection of different strains of HCMV in same tissue also can occur. HCMV infections, including primary and reactivation infections, are generally mild or symptomless in immunocompetent individuals.4 Although HCMV infections in most cells or organs cause no clinical symptoms, it can cause lysis of the target cells and may therefore be amenable to antiviral chemotherapy. HCMV becomes latent after primary infection, and peripheral blood mononuclear cells such as monocytes and T-cells seem to be one of the principal sites of persistent infection. As a constituent of viral envelops, glycoprotein-B is involved in virus-cell receptor interactions and serve as target antigens for the MHC class I-restricted CD8 cytotoxic T lymphocytes. However, as Meyer-König reports,1 a defined HCMV glycoprotein-B strain may not necessarily protect from superinfection with a different strain of simultaneous primary infection with other glycoprotein-B strains. DNA amplification with PCR and of restriction-fragment-length polymorphism is a useful method for molecular epidemiological studies of HCMV infection. Differences of pathogenicity between HCMV strains are still controversial. *Kei Numazaki, Masami Ikehata, Hideomi Asanuma, Shunzo Chiba Departmentof Paediatrics, Sapporo Medical University School of Medicine, Sapporo 060-8543, Japan 1
2
3
4
Meyer-König U, Ebert K, Schrage B, Pollak S, Hufert FT. Simultaneous infection of healthy people with multiple human cytomegalovirus strains. Lancet 1998; 352; 1280–81. Chou S, Dennison KM. Analysis of interstrain variation in cytomegalovirus glycoprotein B sequences encoding neutralization-related epitopes. J Infect Dis 1989; 166: 604–07. Shepp DH, Match ME, Ashraf AB, Lipson SM, Millan C, Pergollizzi R. Cytomegalovirus glycoprotein B groups associated with retinitis in AIDS. J Infect Dis 1996; 174: 184–87. Numazaki K, Chiba S. Current aspects of diagnosis and treatment of cytomegalovirus infections in infants. Clin Diagn Virol 1997; 8: 169–81.
THE LANCET • Vol 352 • November 21, 1998
based medicine, but such an approach seems like a step backward. *Bertil Lindmark, Anders Ottosson Astra Draco AB, Department of Clinical Drug Safety and Epidemiology, PO Box 34, S-221 00 Lund, Sweden 1 2
Jenne JW. Can oral 2 agonists cause heart failure. Lancet 1998; 352: 1081–82. Martin MM, Dunn NR, Freemantle SN, Mann RD. Risk of non-fatal cardiac failure and ischaemic heart disease with long acting 2 agonists. Thorax 1998; 53: 558–62.
Adverse effects of human insulin Sir—With respect to your Aug 29 editorial,1 we represent people with insulin-dependent diabetes who have difficulties with genetically produced human insulin which largely regress with a change to natural animals insulins. These adverse effects have not been generally recognised by the medical profession, and despite the absence of large scale randomised controlled trials human insulin has become first-line treatment. It is noteworthy, however, that in the past year the Medicines Control Agency (MCA) has provided more information and in a more helpful way. We believe that there are several possible reasons for this change: a policy of open government; the threat of a Freedom of Information Act; the fact that we can often obtain information from the European Evaluation Agency; or a change in government or staff. The information held by the MCA from premarketing trials would be of real benefit in evaluating the adverse reactions to human insulin, but we have been unable to elicit these data from the MCA in more than 4 years. During our lobbying for a change in the Medicines Act 1968 to allow freedom of information to apply to medicines, we received a letter from the Baroness Hayman, dated Aug 19, 1998, stating that “The CSM concluded that some patients did experience problems with human insulin, particularly when initially transferred from animal insulins, and were better suited to continuing their treatment with animal insulins”. At no time during our years of correspondence with the MCA has such a statement been made, even though the number of reported adverse reactions to human insulin is more than five times greater than for the combined total for bovine and porcine insulins. Nor is there evidence that human insulin has any greater benefit than animal insulins. Further, omitting to make public the CSM conclusions has
1710
resulted in a failure to address the cost/benefit relation in the prescribing of insulins. In 1995, we pointed out to the Department of Health that our conservative estimate for prescribing human insulin was costing the NHS an extra £19 million per year. This figure has clearly risen since then with the introduction of disposable pens for human insulin, and with the cost of treating the adverse reactions. This selective provision of information by the MCA and failure to make public the information they have affects not only the health and wellbeing of patients but also the public purse at a time when our health service is struggling financially. Jenny Hirst Insulin Dependent Diabetes Trust, PO Box 294, Northampton NN3 2BN, UK 1
Anon. Freedom of information, when it suits. Lancet 1998; 352: 665.
Simultaneous infection of immunocompetent individuals with multiple cytomegalovirus strains Sir—Ursula Meyer-König and colleagues (Oct 17, p 1280)1 report that several human cytomegalovirus (HCMV) glycoprotein-B variants might be latent in different tissue of one healthy individual and that the analysis of HCMV strain variability at a single site of the glycoprotein-B gene was insufficient. However, the clinical importance of latent simultaneous infection of healthy people with multiple HCMV strains remains unclear. HCMV has been classified into four glycoprotein-B genotypes, according to restriction-fragment-length polymorphism of the variable site of the gene.2 Viraemia caused by glycoproteinB group 2 HCMV strain was associated with higher risk of HCMV retinitis than viraemia due to other glycoprotein-B groups.3 We analysed 33 clinical isolates of HCMV from immunocompetent children less than 2 years of age. HCMV from urinary samples was isolated by the standard tissue-culture technique that uses MRC-5 cells. The presence of HCMV was confirmed by observation of its characteristic cytopathic effect and by immunofluorescent staining with monoclonal antibodies against HCMV immediateearly and early antigen. DNA was extracted from MRC-5 cells, and we amplified HCMV glycoprotein-B gene with PCR assay according to Chou’s
method.2,3 The amplified fragment that contained glycoprotein-B gene was digested in parallel with two endonucleases, Hha I and Rsa I. Among 33 clinical isolates, 24 were identified as glycoprotein-B group 1, one as group 2, six as group 3, and two as simultaneous infection of group 1 and group 3. We did not identify glycoprotein-B group 4 from our samples. There were no differences in clinical appearances between HCMV glycoprotein-B groups 1 to 3. Simultaneous infection of different strains of HCMV in same tissue also can occur. HCMV infections, including primary and reactivation infections, are generally mild or symptomless in immunocompetent individuals.4 Although HCMV infections in most cells or organs cause no clinical symptoms, it can cause lysis of the target cells and may therefore be amenable to antiviral chemotherapy. HCMV becomes latent after primary infection, and peripheral blood mononuclear cells such as monocytes and T-cells seem to be one of the principal sites of persistent infection. As a constituent of viral envelops, glycoprotein-B is involved in virus-cell receptor interactions and serve as target antigens for the MHC class I-restricted CD8 cytotoxic T lymphocytes. However, as Meyer-König reports,1 a defined HCMV glycoprotein-B strain may not necessarily protect from superinfection with a different strain of simultaneous primary infection with other glycoprotein-B strains. DNA amplification with PCR and of restriction-fragment-length polymorphism is a useful method for molecular epidemiological studies of HCMV infection. Differences of pathogenicity between HCMV strains are still controversial. *Kei Numazaki, Masami Ikehata, Hideomi Asanuma, Shunzo Chiba Departmentof Paediatrics, Sapporo Medical University School of Medicine, Sapporo 060-8543, Japan 1
2
3
4
Meyer-König U, Ebert K, Schrage B, Pollak S, Hufert FT. Simultaneous infection of healthy people with multiple human cytomegalovirus strains. Lancet 1998; 352; 1280–81. Chou S, Dennison KM. Analysis of interstrain variation in cytomegalovirus glycoprotein B sequences encoding neutralization-related epitopes. J Infect Dis 1989; 166: 604–07. Shepp DH, Match ME, Ashraf AB, Lipson SM, Millan C, Pergollizzi R. Cytomegalovirus glycoprotein B groups associated with retinitis in AIDS. J Infect Dis 1996; 174: 184–87. Numazaki K, Chiba S. Current aspects of diagnosis and treatment of cytomegalovirus infections in infants. Clin Diagn Virol 1997; 8: 169–81.
THE LANCET • Vol 352 • November 21, 1998